Human fetal hemoglobin (HbF) differs from HbA in both functional and structural aspects. These differences are evidenced by the weaker affinity of HbF for 2,3 diphosphoglyceric acid, and by the non-participation of HbF in gel formation with HbS. The molecular basis of these differences is not clear. There are 39 amino acid differences between the gamma chains of HbF (alpha 2 gamma 2) and the beta chains of HbA (alpha 2 beta 2), several of which are found in the 2,3 diphosphoglyceric acid binding site. A number of other amino acid substitutions are clustered in one exposed helical region of the gamma chain. We are using solid phase synthesis to reproduce this helical region. Immunoabsorption with this synthetic peptide of an antiserum to HbF is being used in an attempt to obtain non-precipitating antibodies specific for this region which do not crossreact with HbA or other hemoglobins. A radioimmunoassay using (14C)-carbamoylated HbF will be used to assess the specificity of binding. We have also obtained crystals of met-HbF of suitable size for X-ray diffraction studies. The specific antibodies and X-ray studies will give information on the conformational and surface structural characteristics of HbF. In addition the antibodies may be useful in quantitating small amounts of HbF in standard laboratory procedures and in prenatal diagnosis of hemoglobinpathies.